This project combines the techniques of genetics and molecular biology to study the behavior of transposable elements in Drosophila melanogaster. Part of the research plan concerns transposable P elements, which cause a syndrome of germ-line aberrations called hybrid dysgenesis. These aberrations include frequent mutation and chromosome breakage. The other part of the plan concerns the L factor, a transposable element postulated to explain the properties of an unstable X chromosome. This chromosome mutates at a high rate, accumulates rearrangements, and has the ability to confer these properties on other, previously stable X chromosomes. This last phenomenon is called chromosome destabilization. The first part of the research plan aims specifically to study the structure and behavior of P elements and to investigate the ways in which they mutate genes and rearrange chromosomes. This will involve molecular cloning of P elements from two Drosophila strains, structural characterization of these elements by restriction mapping, and localization of the elements in the genome by in situ hybridization. When these aims are accomplished, various mutations and chromosome rearrangements that involve the cloned elements will be analyzed. Genetic experiments will also be conducted to study the in vivo behavior of several P elements isolated by recombination from a single Drosophila strain. Another objective is to study the relationships among three dysgenic traits in hybrids made by crossing inbred wild strains with standard laboratory testers. The second part of the plan aims to define the conditions affecting L factor activity. The methodology will consist of genetic analysis only. The various experiments of the plan concern sex differences, cytoplasmic regulation, autosomal influences, stochastic factors, and genetic control. There will be a special emphasis on the study of chromosome destabilization. Transposable elements constitute a significant fraction of the genome of several eukaryotes. Their ubiquity suggests that they exist in humans as well. These elements cause mutations, break chromosomes, regulate genes, and may be related to some of the oncogenic viruses. It is possible that their transpositional activity causes some human cancers. This research plan aims to study two types of transposable elements in Drosophila melanogaster, which, by virtue of its well-developed genetics, polytene chromosomes and a growing fund of molecular information, is an excellent experimental organism.